Computational modeling of protein assemblies

Abstract

Computational methods to predict the 3D structures of protein interactions fall into 3 categories—template based modeling, protein–protein docking and hybrid/integrative modeling. The two most important considerations for modeling methods are sampling and scoring conformations. Sampling has benefitted from techniques such as fast Fourier transforms (FFT), spherical harmonics and higher order manifolds. Scoring complexes to determine binding free energy is still a challenging problem. Rapid advances have been made in hybrid modeling where experimental data are amalgamated with computations. These methods have received a boost from the popularity of experimental methods such as electron microscopy (EM). While increasingly larger and complicated complexes are now getting elucidated by integrative methods, modeling conformational flexibility remains a challenge. Ongoing improvements to these techniques portend a future where organelles or even cells could be accurately modeled at a molecular level.